Evidence map›Paper›PMID 31573406›Full record

ArticleCirculation research2019

An Unbiased Proteomics Method to Assess the Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Wenxuan Cai, Jianhua Zhang, Willem J de Lange, Zachery R Gregorich, Hannah Karp, Emily T Farrell, Stanford D Mitchell, Trisha Tucholski, Ziqing Lin, Mitch Biermann and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 82 citations in OpenAlex.

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  14. A transcriptional enhancer regulates cardiac maturation.Nature cardiovascular research · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Wenxuan CaiFrom the Molecular and Cellular Pharmacology Training Program (W.C., S.D.M., T.J.K., Y.G.), University of Wisconsin-Madison.
Jianhua ZhangDepartment of Medicine (J.Z., Z.R.G., M.B., T.J.K.), University of Wisconsin-Madison.
Willem J de LangeDepartment of Pediatrics (W.J.d.L., E.T.F., J.C.R.), University of Wisconsin-Madison.
Zachery R GregorichDepartment of Cell and Regenerative Biology (W.C., Z.R.G., H.K., S.D.M., Z.L., T.J.K., Y.G.), University of Wisconsin-Madison.
Hannah KarpDepartment of Cell and Regenerative Biology (W.C., Z.R.G., H.K., S.D.M., Z.L., T.J.K., Y.G.), University of Wisconsin-Madison.
Emily T FarrellDepartment of Pediatrics (W.J.d.L., E.T.F., J.C.R.), University of Wisconsin-Madison.
Stanford D MitchellFrom the Molecular and Cellular Pharmacology Training Program (W.C., S.D.M., T.J.K., Y.G.), University of Wisconsin-Madison.
Trisha TucholskiFrom the Molecular and Cellular Pharmacology Training Program (W.C., S.D.M., T.J.K., Y.G.), University of Wisconsin-Madison.
Ziqing LinDepartment of Cell and Regenerative Biology (W.C., Z.R.G., H.K., S.D.M., Z.L., T.J.K., Y.G.), University of Wisconsin-Madison.
Mitch BiermannDepartment of Medicine (J.Z., Z.R.G., M.B., T.J.K.), University of Wisconsin-Madison.
Sean J McIlwainDepartment of Biostatistics and Medical Informatics (T.T., S.J.M.), University of Wisconsin-Madison.
J Carter RalpheDepartment of Pediatrics (W.J.d.L., E.T.F., J.C.R.), University of Wisconsin-Madison.
Timothy J KampFrom the Molecular and Cellular Pharmacology Training Program (W.C., S.D.M., T.J.K., Y.G.), University of Wisconsin-Madison.
Ying GeFrom the Molecular and Cellular Pharmacology Training Program (W.C., S.D.M., T.J.K., Y.G.), University of Wisconsin-Madison.
Highland Community College - Illinois · US

Funding

WATER DISTRIB:PHYSICAL PROPERT:PIZZA &LMPS MOZZARELLA CHEESES:EARLY STAGE MATURP41RR002301 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 1985 to 2011
$13.0M
Training Program in Translational Cardiovascular Science (TPTCS)T32HL007936 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Gail A Robertson · 2001 to 2026
$11.6M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
Chemistry-Biology Interface Training ProgramT32GM008505 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BLACKWELL, HELEN E. · 1993 to 2023
$9.8M
Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Deciphering Myofilament Modifications in Ischemic CardiomyopathyR01HL109810 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2013 to 2024
$3.5M
Top Down Proteomics Of Myofilaments In Heart FailureR01HL096971 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2011 to 2021
$3.3M
Enabling Top-Down Proteomics through Materials Chemistry and NanotechnologyR01GM117058 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING, JIN, SONG · 2015 to 2023
$2.7M
Ultra High Resolution Mass Spectrometer for Biomedical ResearchS10OD018475 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2015 to 2015
$2.0M
Refining Cardiac Progenitor Cells for Myocardial RepairR01HL129798 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI KAMP, TIMOTHY J. · 2015 to 2018
$1.5M
MASH Explorer, a Comprehensive Software Environment for Top-Down ProteomicsR01GM125085 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2018 to 2021
$1.2M
NCRR NIH HHS P41 RR002301NHLBI NIH HHS F30 HL126452NHLBI NIH HHS R01 HL096971NHLBI NIH HHS R01 HL109810NHLBI NIH HHS R01 HL129798NHLBI NIH HHS T32 HL007936NHLBI NIH HHS U01 HL134764NHLBI NIH HHS U01 HL148690NIGMS NIH HHS R01 GM117058NIGMS NIH HHS R01 GM125085NIGMS NIH HHS T32 GM008505NIGMS NIH HHS T32 GM008688NIGMS NIH HHS T32 GM008692NIH HHS S10 OD018475
6 · The paper itself

Abstract

rationaleHuman pluripotent stem cell (hPSC)-derived cardiomyocytes exhibit the properties of fetal cardiomyocytes, which limits their applications. Various methods have been used to promote maturation of hPSC-cardiomyocytes; however, there is a lack of an unbiased and comprehensive method for accurate assessment of the maturity of hPSC-cardiomyocytes.

objectiveWe aim to develop an unbiased proteomics strategy integrating high-throughput top-down targeted proteomics and bottom-up global proteomics for the accurate and comprehensive assessment of hPSC-cardiomyocyte maturation. METHODS AND

resultsUtilizing hPSC-cardiomyocytes from early- and late-stage 2-dimensional monolayer culture and 3-dimensional engineered cardiac tissue, we demonstrated the high reproducibility and reliability of a top-down proteomics method, which enabled simultaneous quantification of contractile protein isoform expression and associated post-translational modifications. This method allowed for the detection of known maturation-associated contractile protein alterations and, for the first time, identified contractile protein post-translational modifications as promising new markers of hPSC-cardiomyocytes maturation. Most notably, decreased phosphorylation of α-tropomyosin was found to be associated with hPSC-cardiomyocyte maturation. By employing a bottom-up global proteomics strategy, we identified candidate maturation-associated markers important for sarcomere organization, cardiac excitability, and Ca

conclusionsWe established an unbiased proteomics method that can provide accurate and specific assessment of the maturity of hPSC-cardiomyocytes and identified new markers of maturation. Furthermore, this integrated proteomics strategy laid a strong foundation for uncovering the molecular pathways involved in cardiac development and disease using hPSC-cardiomyocytes.

Indexed as

Cell DifferentiationChromatography, LiquidSpectrometry, Mass, Electrospray IonizationTandem Mass SpectrometryBiasCell Culture TechniquesCell LineHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsMyocytes, CardiacPhenotypeProteinsProteomicsReproducibility of ResultsTime FactorsProteinsheartmass spectrometrypluripotent stem cellsproteomicstroponin

Identifiers

PMID31573406
PMCPMC6852699
OpenAlexW2978210721

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.